The central goal of this project is to advance the therapeutic applications and the development of an exciting novel neuroprosthetic technology, Safe Direct Current Stimulation (SDCS). Direct current (DC) compared to biphasic charge balanced pulses normally used by neural prostheses to interface to the nervous system, can more naturally control neural activity. Unlike biphasic current pulses used to excite neurons, DC can excite, inhibit, and modulate sensitivity of neurons. However using DC for implantable prosthetic applications has not been possible due to the DC's inherent violation of the charge injection safety constraints at the metal electrode interfaces. Safe DC overcomes these constraints and opens a new avenue for research into exciting possibilities of using DC to interface to the nervous system. We will optimize the use of safe DC to improve the performance of a vestibular prosthesis for those suffering from balance disorders. Vestibular prostheses encounter difficulty encoding head motion away from the implanted vestibular labyrinth because encoding this motion requires inhibition of spontaneous activity of the nerve. We obtained preliminary data in a chinchilla animal model showing that modulating the amplitude and polarity of safe DC could encode both ipsilateral and contralateral head rotations. Here we propose to understand and overcome the hurdles that we encountered in our preliminary experiments stemming from the key safe DC stimulation challenge: the reversal of neural response as a function of increased safe DC intensity. That is, anodic (positive) stimulation causes inhibition at low DC intensities but excitation at higher intensities; and cathodic (negative) stimulation causes excitation at low DC intensities but inhibition as the amplitude increases. In the vestibular prosthetic stimulation this effect imposes a limit on the velocity of encoding head motion. We also propose to advance the SDCS technology by identifying and solving the key technical challenges with a miniaturized SDCS to improve longevity and power consumption. Aim 1) Improve the vestibular prosthetic encoding of head motion. We will investigate the origin of the response reversal and improve the head velocity encoding by eliminating or reducing the reversal with a bipolar stimulation paradigm. Aim 2) Examine the safety of SDCS. We will examine the physiological and histological limits of safe DC stimulation in chinchillas stimulated for 60 days. Aim 3) Address key technical challenges associated with longevity and low power consumption of the miniaturized SDCS.